Project Summary This project includes both development of advanced MRI sequences to study brain stiffness as well as a clinical application of this technique to study brain health in children with autism. Currently 1 in 88 children in the United States are diagnosed with autism. Autism is characterized by physical and neurological deficits often including changes in regional brain volume. This indicates that brain development may be affected by autism and contributes to its clinical and behavioral expression. However, autism causality is largely unknown making it challenging to diagnose autism, assess severity, and provide quantitative metrics for rehabilitation. Investigation of brain health in people with autism has been limited, as in vivo assessments of microstructural properties are challenging in such a population. One technique is magnetic resonance elastography (MRE), which is the first noninvasive, sensitive, repeatable neuroimaging technique capable of generating mechanical property measurements for assessing brain microstructural health. Brain mechanical properties are affected by neurodegenerative disease, and recently, global brain integrity deficits in children with cerebral palsy have been observed. MRE measures are sensitive to even subtle individual differences in brain health, that relate to cognitive function, aerobic fitness or response to intervention and therefore, brain tissue viscoelasticity, measured with MRE, can quantify how neural tissue microstructure affects the social, linguistic, and developmental delays seen in children with autism. Brain stiffness in children with autism, however, has never been studied in vivo. The objective of this research is to use MRE to study brain health in children with autism and to understand how these brain mechanical properties are related to functional measures such as cognitive skills, linguistic skills, and behavior. Accomplishing this goal will provide a framework for diagnosis and intervention in this population. However, MRE is an inherently long MRI technique, and it requires a subject to lay still for an extended period of time in a small space, which makes it very challenging to perform this scan in children with disabilities. We are prepared to implement faster scan times to optimally tailor our MRE acquisition toward children with autism. Due to the need to capture tissue deformation in multiple directions over time, MRE is highly spatiotemporally redundant, and can be modeled as a low rank problem for accelerated imaging. To do this we will design a spatiotemporal data under-sampling technique, called OSCILLATE, and the k-space data will be reconstructed with a low rank joint image reconstruction across all sampled time points. Upon successful completion of this project we will have quantified brain mechanical differences in subjects with classic autistic disorder to provide basis for diagnosis and intervention. We will have established a novel protocol for faster MRE acquisition for use in studying any child with atypical neurological development. Our team is in an unparalleled position of facilities, research contacts, MRE technical development experience and pediatric MRE experience to carry out this research.